11-ketotestosterone, 11-keto-19-nortestosterone, esters thereof and process



United States Patent ll-IETOTESTOSTERONE, 11-KETO-19-NORTES- TOSTERONE,ESTERS THEREOF AND PROCESS Frederick W. Heyl, Kalamazoo, and Milton E.Herr,

Kalamazoo Township, Kalamazoo County, Mich., assignors to The UpjohnCompany, Kalamazoo, Micln, a corporation of Michigan No Drawing.Application January 15, 1953, Serial No. 331,495

14 claims. (Cl. zen-391.45

The present invention relates to steroids of the androstane andIO-normethylandrostane series and is more particularly concerned withll-ketotestosterone, -normethyl-1l-ketotestosterone, their 17-esters anda process for the production thereof.

The process and products of the present invention may be illustrativelyrepresented by the following formulae:

wherein R is hydrogen or methyl and wherein R is hydrogen or the acylradical of a carboxylic acid containing from one to eight carbon atomsinclusive, especially those acids selected from the group consisting ofaliphatic acids, carbocyclic acids and aromatic acids.

The process of the present invention consists in oxidizing a 17,8-esterof llfi-hydroxytestosterone or 10-normethyl-llfl-hydroxytestosteronewith chromic acid, either as such or as generated in situ to obtain thecorresponding 7,3-acy1oXy-1l-ketotestosterone or17p-aoyloxy-10-normethyl-1l-ketotestosterone. Hydrolysis of these esterswith base yields ll-ketotestosterone or 10-normethy1-11-ketotestosterone, respectively.

it is an object of the present invention to provide 11-ketotestosterone, lO-normethyl-ll-ketotestosterone and esters thereof.Another object of the present invention is the provision of a processfor the production of '11- ketotestosterone,lO-normethyl-ll-ketotestosterone, and esters thereof. Other objects ofthe invention will be apparent to one skilled in the art to which thisinvention pertains.

ll-ketotestosterone and its esters as well as IO-normethylll-ketotestosterone and esters thereof demonstrate androgenic hormonaland adrenocortical activity. These compounds have a pronounced anaboliceffect.

The starting compounds of this invention, i. e., the 17/3-esters ofllfl-hydroxytestosterone and 10-normethyl- 11 fi-hydroxytestosterone,are prepared by heating adrenosterone or IO-normethyladrenosterone(Preparation 2A) with a secondary amine, for example, piperidine,pyrrolidine, N-methyl-toluidine, dibenzylamine, diethylamine,dicyclohexylamine or other like amine, with pyrrolidine being preferred,to yield the corresponding S-enamine, such as3-(N-pyrrolidyl)-3,5-androstadiene-l1, 17-dione,3-(N-piperidyl)-3,5-androstadiene-11,17-dione, 3-(N-dibenzylamine)-10normethyl 3,5 androstadiene 11,17 dione, 3-(N-diethylamine)-10-normethyl3,5 androstadiene-11,l7-dione, and other like enamines. The thusobtainedenamines are then reduced, preferably with a metallic hydride, such aslithium aluminum hydride or sodium borohydride, to yield thecorresponding 1lB,17[3- diols which by hydrolysis givellfi-hydroxytestosterone and IO-normethyl-llfi-hydroxytestosterone.Treatment of llfi-hydroxytestosterone or10-normethy1-1lp-hydroxytestosterone with an acylating agent, such as ananhydride of an organic carboxylic acid or an acyl halide wherein theacyl group is the acyl radical of an organic carboxylic acid and whereinthe organic carboxylic acid in either case preferably contains from oneto eight carbon atoms inculsive, results in the corresponding l7-ester.The formic acid esters of llfl-hydroxytestosterone orIO-normethyl-1lfl-hydroxytestosterone are obtained by mixing thesecompounds with formic acid.

Representative starting compounds, thus prepared, include:IZB-tormoXy-llfi-hydroxytestosterone, 17/8-acetoxy-llfl-hydroxytestosterone, 17,8-propion0xy 11B hydroxytestosterone,17,8-butyroxy-1lp-hydroxytestosterone,17p-va1eroxy-1lfl-hydroxytestosterone, 17B-heXan0yloXy- 1 1fl-hydroxytestosterone, l7 3-heptanoyl0Xy-1 lfi-hydroxytestosterone,17/3-octanoy1oxy 11 8 hydroxytestosterone,17fl-benzoyloxy-1LB-hydroxytestosterone,l7fi-phenylacet0Xy-1lfi-hydroxytestosterone, 17,8 (fl-cyclopentyl)propionoxy-l lfi-hydroxytestosterone, 17fi-formoxy 10normethyl-1IB-hydroxytestosterone, 17,8 acetoxy 10normethyl-1lfi-hydroxytestosterone, 173-propionoxy-10-normethyl-11,3-hydroxytestosterone, 17,8-butyroxy 1Onormethyl-1lfi-hydroxytestosterone, 17 p-valeroxy 10normethyl-1lp-hydroxytestosterone, 17,8 hexanoyloxyl 10- methylllfi-hydroxytestosterone, l7fi-heptanoyloxy-10- normethyl-1lfi-hydroxytestosterone, 17 8-octanoyloXy-10-normethyl-1lo-hydroxytestosterone, l7fi-benzoyloxy 10- normethyl-11,6hydroxytestosterone, l7 phenylacetoxy- 10-normethyl-11Bhydroxytestosterone, 17 3 18 cyclopentyl) propionoxy 10 normethylhydroxytestosterone, and other like compounds.

In carrying out the process of the present invention, the selected1lfi-hydroxytestosterone-17-ester or the selected 10-normethyl-113-hydroxytestosterone17-ester, dissolved in an organic solvent such asacetic acid, benzene, toluene, petroleum ether, heXanes (Skellysolve B),dioxane or similar like solvent, with acetic acid preferred, is oxidizedwith a solution containing chromic acid. The chromic acid may be addedas chromic acid anhydride together With a small but sufficient amount ofwater to produce the dichromate ion (CI2O7'), or may be produced in situby the reaction between an alkali metal dichromate such as sodium orpotassium dichromate and an acid, for example, acetic acid, formic acid,or sulfuric acid. The reaction may be carried out in a heterogeneous ora homogeneous system. It the reaction is carried out in a heterogeneoussystem, the llfi-hydroxytestosterone-17- ester or thel0-normethyl-llB-hydroxytestosterone-17- ester, dissolved in an organicsolvent which is inert to oxidation under the reaction conditions suchas benzene, chlorobenzene, hexane, chloroform, or a similar solvent, isadmixed with a solution of aqueous sodium dichromate or potassiumdichromate acidified with sulfuric acid or sulfuric acid combined Withacetic acid. Vigorous agitation is then employed to bring the organiclayer into intimate contact with the aqueous solution. The reaction timeis mainly dependent on eflicient stirring. In the preferred embodiment--of the invention, the oxidation is carried out in homogeneoussolution, with acetic-acid as solvent and chromic acid as oxidizingagent, the chromic acid being produced by the reaction of small amountsof waterwith chromic anhydride. At the termination of the reaction,excess of chromic acid is destroyed by adding methyl or ethyl alcohol tothe solution and concentrating the solution on a steam bath in vacuo.The temperature of reaction is between about zero and about fiftydegrees centigrade, with temperatures between about fifteen and thirtydegrees centigrade preferred. The reaction time depends on thetemperature and may vary between about one-half hour to about ten hoursor even longer. At room temperature, i. e., at about 25 degreescentigrade, the reaction time is usually between about three and eighthours. The thus obtained111=ketotestosterone 17- ester or IOnormethyl-ll-ketotestosterone-l7-ester.is then purified byrecrystallization, if desired.

To obtain ll-ketotestosterone or 10-normethyl-1leketotestosterone, theesters of these compounds are treated with a base-in an organic solvent,such as methanol, ethanol, tertiary butyl alcohol, dioxane, acetone, orother like solvent. In the preferred embodiment of the invention, the17-ester of ll-ketotestosterone or l-normethylll-ketotestosterone isheated at reflux for a period of about fifteen minutes to one hour with.methanolic or ethanolic sodium or potassium hydroxide, whereaftertheresulting solution is neutralized with a mineral acid. The resultingprecipitate of llrketotestosterone or IO-normethyl-1l-l-zetotestosteronemay be separatedbyfiltration and recrystallized from an organic solvent,such as a methylene chloride-ether mixture.

Thefollowing examples illustrate the process of the present inventionbut arenot to be construed aslimiting.

PREPARATION 1A.-3-(NPYRROLIDYL)-3,5ANDRO- STADIENE-l 1,17-DIONE Amixture of six grams (0.02 mole) of adrenosterone, 160 milliliters ofbenzene, 202 milliliters (0.024 v.rnole) of pyrrolidine and tenmilligrams of ,para-toluenesulfonic acid monohydrate was heated atreflux for agperiodof eighty minutes in a distilling flask-equipped witha water trap. The water formedin the reaction was removed bycodistillation with benzene. The benzene was then removed bydistillation under reduced pressure and the yellow solid residue wastrituratedwithfifty milliliters :of methanol. After cooling,.3.(N-pyrrolidyl) 3,5androstadiene-l 1,17-dione wasrecovered.byfiltratiomand dried in vacuo. The weight .was 6.23 grams, .ayield .of -83 percent. When recrystallized from ether, the :productmelted at 173to 178 degrees centigrade.

Analysis.Calculated for v(-DzsHmNOz:

C, 78.14; H, 884. Found: C, 78.24; H, 8.72.

( 1B) 3-(N-PYRROLLDYI.)-3,5:ANDROSTADIENE- 1 1,8,17,8-DIOL A solution of6.23 grams of 3-(N-pyrrolidyl)-3,5-andro stadiene-11,17-dione, dissolvedin 100 milliliters of anhydrous tetrahydrofuran, was added over a periodof five minutes, with stirring, to a mixture of 3.34 grams of lithiumaluminum hydride in 900 milliliters of anhydrous ether. The reactionmixture was refluxed for aperiod of five minutes, whereafter thereaction vessel was cooled in an ice bath. The metal complex was thendecomposed by the cautious addition of six milliliters of water. Theorganic layer was decanted througha fluted filter and the clear ethersolution. thus obtained, was washedwith water, dried over anhydroussodium sulfate and evaporated to yield 5.26 grams of3-(N-pyrrolidyl)-3,5-androstadiene- 11,8,1'7B-diol. Infrared analysisconfirmed the postulated structure of the enamine diol.

(1C) 11 B-HYDROXYTESTOSTERONE Five and twenty-six hundredths grams (5.26grams) of 3-(N-pyrrolidyl) 3,5-androstadiene-11,3,17 3-diol, eight *4grams of sodium acetate, ten milliliters of water, four milliliters ofacetic acid and -milliliters of methanol were refluxed for a period offive hours. Upon cooling, 750 milliliters of ether Was added and thesolution washed with dilute sodium carbonate solution, water, and thendried over anhydrous sodium sulfate. Upon evaporation of the ether,3.02-grams of crude llfi-hydroxytesterone was obtained. Repeatedrecrystallizationifrom ethyl acetate gave a product of constant meltingpoint; 241 degrees Centigrade. Extraction of the aqueous alkalinewashings with ether-benzene mixturesand chloroform resulted in anadditional 0.93 gram of crystalline material which was chromatographed.together with material from the mother liquor or the firstcrystallization, over a column of activated alumina. A total of 3.3grams equal to a yield of 55 percent of pure llfi-hydroxytestosteronewas obtained.

( 1D) 1 lfi-HYDROXYTESTOSTERONE-17-ACETATE A solution of 0.91 gram'ofllfi hydroxytestosterone, dissolved in sixniilliliters of'driedand-redistilled pyridine, wastreated with'six milliliters of aceticanhydridc. .After standing at room temperature for 'seventeen hours, itwas poured into ice water. The'mixturewas filtered after two hours ofstanding and the precipitatewas washed with=water and dried invacuo. Thecrude'yield was 88 percent. 5 Upon recrystallization from anether-hexane mixture, pure 1lfi-hydroxytestosterone-17-acetate ofmelting point l' 50rdegrees centigrade was obtained.

( 1 E) 1 1}3-HYDROXYTESTOSTERONE17-PROPIONATE In the same manner asgiven iii-Preparation ID, by the reaction of llfl-hydroxytestosteroneand propionic anhydride, 11 3-hydroxytestosterone-17-propionate wasobtained in 94 percent yield. The melting point of this compound was 154to 155 degrees centigrade.

(1F) 1 lfi-HYDROXYTESTOSTERONE-17-BENZOATE Thirty hundredths gram (0.30gram) of llfi-hydroxytestosterone, suspended in twelve milliliters ofdry benzene, was treated with 0.32 milliliter of distilled benzoylchloride and 0.32 milliliter of dry pyridine. The mixture was stirredfor seventeen hours at room temperature during which time the benzoatewas deposited from the solution. After refrigeration,.the product wascollected on a filter, washed with benzene and ether, and then dried.The crude yield was 0.36 gram (ninety percent). Recrystallized fromethyl acetate, llfi-hydroxytestosterone- 17-benzoate melted at 287degrees centigrade.

In the .same manner asgiven in Preparations 1D, 1E and IF, the43-.cyclopentylpropionate, .butyrate, isobutyrate, 'valerate,isovalerate, hexanoate, heptanoate, oetanoate, phenylacetate, and .otherlike -17-esters .of 11:,8-hydroxytestosterone may=be prepared byreaction of 11phydroxytestosterone and :the selected acid anhydride orhalide. Treatment 'LOf 11 fifhydroxytestosterone with formic. acidresults in 1lfi-hydroxytestosterone-17-formate.

PREPARATION 2A.--1 O-NORMETHYLADRENOSTERONE A medium of sixty grams ofvEdamine enzymatic digest of lactalbumin, nine grams of corn steepliquor and grams of technical dextrose diluted to three liters with tapWater, adjusted to a pH of 4.3 to 4.5 and sterilized, was inoculatedwith Rhizopus nzfgricans minus strain, American Type Culture CollectionNumber 6227b, and incubated .for .24 hours at a temperature of 28degrees centigrade using a rate of aeration and stirring such thatthe-oxygen uptake was-6.3 to 7 millimoles per hour per liter of NazSOsaccording to the method of Cooper et al., Ind. Eng. .Chem., 36,504(1944). To this medium containing a 24-hour growth of Rhizopusnigricans minus strain wasadded 1.5 grams'of l0enormethyltestosteroneEBirch, J. Chem. Soc. (London) .1950, 367] in thirty millilitersrofabsolute ethanol to providea suspension of the steroid inzthe culture.After an additional 24 hour period of incubation under the sameconditions of'temperature and aeration, the beer and mycelium wereextracted. The mycelium was filtered, washed with acetone and extractedwith methylene chloride. The acetone and methylene chloride extractsincluding solvent were added to the beer filtrate. The mixed extractsand beer filtrate were repeatedly extracted with methylene chloride andthe combined extracts were washed with two percent aqueous solution ofsodium bicarbonate and then with water. After drying the methyleneextracts over anhydrous sodium sulfate, the solvent was removed byevaporation in vacuo. The residue was decolorized by treatment of themethylene dichloride solution with Magnesol (synthetic magnesiumsilicate). After removal of the solvent, the material waschromatographed over alumina in benzene solution and the thus-obtainedmaterial was repeatedly recrystallized from ethyl acetate to givesubstantially pure l-normethyl-1lot-hydroxytestosterone.

Two and nine tenths grams (2.9 grams) (0.01 mole) of-normethyl-1lot-hydroxytestosterone thus-obtained were dissolved inforty milliliters of benzene and thereto'was added with cooling asolution of ten grams (0.034 mole) of crystalline sodium dichromate ineight milliliters of acetic acid, 13.5 milliliters of concentratedsulfuric acid and 35 milliliters of water. The mixture was stirred forsix hours at 25 to thirty degrees centigrade. The benzene solution wasthen separated, washed with 25-milliliter portions of water andconcentrated to dryness in vacuo. The material,10-normethyladrenosterone, was recrystallized from aqueous ethanol.

(28) 3-(N-PYRROLIDYL)-3,5ESTRADIENE-11,17-DIONE Substituting10-normethyladrenosterone for adrenosterone in the synthesis ofPreparation 1A resulted in 3- (N-pyrrolidyl -3,5-estradiene-l l,l7-dione. I

(2C) 3-(N-PYRRQLIDYL)-3,5-as'rRxn1aNn-l13,17,8-DIOL In the same manneras given in Preparation 1B, 3-(N- pyrrolidyl)-3,5-estradiene-11,17-dionewas reduced with lithium aluminum hydride in ether-tetrahydrofuransolution to give 3-(N-pyrrolidyl)-3,5-estradiene-11 3,17/3-diol.

(2D) IO-NORMETHYL-l 1 fi-HYDROXYTESTOSTERONE Hydrolysis of3-(N-pyrrolidyl)-3,5-estradiene-l118,175- diol with acetic acid andsodium acetate in methanol in the manner given in Preparation 1Cresulted in IO-normethyl-1 1 B-hydroxytestosterone.

(2E) IO-NORMETHYL-l lfi-HYDROXYTESTOSTERONE-17- ACETATE In the samemanner as given in Preparation 1D, 10-normethyl-ll 8-hydroxytestosteronewas treated with acetic anhydride in pyridine to giveIO-normethyl-llfl-hydroxytestosterone-17-acetate.

(2F) 10NORMETHYL-l 1/3-HYDROXYTESTOSTERONE-17- PROPIONA'IE Treatingl0-normethyl-llfi-hydroxytestosterone in pyridine solution withpropionic anhydride at room temperature in the manner of Preparation 1Eyielded 10-normethyl-1 1p-hydroxytestosterone-17-propionate.

(2G) IO-NORMETHYL-l lfl-HYDROXYTESTOSTERONE- l 7- ([3-CYCLOPENTYL-PROPIONATE Treatment of 10-normethyl-llfi-hydroxytestosterone withB-cyclopentylpropionyl bromide in benzene solution in the presence of asmall amount of pyridine gave 10- normethyl-l lfi-hydroxytestosterone 17(fi-cyclopentyl) propionate.

In the same manner as given in Preparations 2E, 2F, and 2G,lO-normethyl-llfi-hydroxytestosterone-17-esters of other acids areprepared by the reaction of l0-normethyl-1lfl-hydroxytestosterone withacid anhydrides or halides, such as, for example, the acetate, butyrate,isobutyrate, valerate, isovalerate, hexanoate, heptanoate, octanoate,benzoate, phenylacetate, and other like esters ofl0-normethyl-llB-hydroxytestosterone. Treatment ofIO-normethyl-Ilfi-hydroxytestosterone with formic acid results in10-normethyl-1 lp-hydroxytestosterone formate.

Example 1.-11-ket0test0sterone propionate A solution of 1.48 grams ofllfi-hydroxytestosteronel7-propionate (Preparation 1E) and eightymilliliters of acetic acid was treated with a solution of 0.74 gram ofchromic acid anhydride in four milliliters of water and eightymilliliters of acetic acid and allowed to stand at room temperature forfive hours. The excess of chromic acid was destroyed by the addition often milliliters of methanol and the solution was concentrated in vacuoon a water bath. The residue, after trituration with water, wasextracted with ether and the ether solution washed with dilute sodiumhydroxide solution and water, and then dried over anhydrous sodiumsulfate. Upon evaporation of the ether there was obtained 1.29 grams ofcrystalline 1l-ketotestosterone-17-propionate equal to a yield of 87percent. 1l-ketotestosterone-l7-propionate, when recrystallized fromether-hexane (Skellysolve B) solution, melted at 139 to 140 degreescentigrade.

Example 2.-11-ket0test0ster0ne acetate A solution of11fl-hydroxytestosterone-17-acetate (Preparation 1D) in benzene wasagitated for 12 hours with an aqueous solution of sodium dichromate andsulfuric acid. The benzene layer was separated from the aqueoussolution, washed, dried over anhydrous sodium sulfate, and evaporated toyield 1l-ketotestosterone-l7-acetate.

In the same manner as given in Examples 1 and 2, 11-ketotestosterone-17-formate, 1l-ketotestosterone-l7-butyrate,1l-ketotestosterone-l7-isobutyrate, ll-ketotestosterone-l7-valerate,1l-ketotestosterone-17-isovalerate, llketotestosterone l7 hexanoate, l1ketotestosterone-17- heptanoate, 1l-ketotestosterone-17-octanoate,ll-ketotestosterone-17-benzoate, 1l-keto testosterone-17-phenylacetate,l l-ketotestosterone-l7-( 3-cyclopentyl)-propionate, and similar likel7-esters of 11-ketotestosterone are prepared by reaction of thecorresponding llfl-hydroxytestosterone-l7ester with chromic anhydride inacetic acid or with an acidified dichromate solution.

Example 3.-1 l -ketotestoster0ne A solution of 1.07 grams of11-ketotestosterone-l7- propionate in fifty milliliters of one Normalmethanolic potassium hydroxide solution containing three milliliters ofwater was refluxed for a period of thirty minutes. The solution waspoured onto ice and the mixture neutralized with dilute sulfuric acid.After standing, the resulting precipitate was recovered, washed withwater and dried. The aqueous filtrate was extracted with methylenechloride to recover an additional amount of material. The total yieldamounted to 97 percent. ll-ketotestosterone when recrystallized frommethylene chloride melted at 187 to 188 degrees centigrade.

Analysis.Calculated for CmHzeOs: C, 75.46; H, 8.67. Found: C, 75.63; H,8.57.

In the same manner, hydrolysis of other esters of 11- ketotestosteronesuch as the formate acetate, butyrate, isobutyrate, valerate,isovalerate, hexanoate, heptanoate, octanoate, fi-cyclopentylpropionate,benzoate, phenylacetate, and similar esters of ll-ketotestosterone withalkalimetal hydroxides such as sodium hydroxide or potassium hydroxidein methanol, ethanol, acetone, tertiary butyl alcohol, dioxane or othersolvent is also productive of ll-ketotestosterone.

Example 4 .--I O-normethyl-I 1 -ket0test0ster0ne propionate Oxidation of10-normethyl-l1/3-hydroxytestosterone- 17-propionate (Preparation 2F) inthe manner shown in Example 1, yielded IO-normethyl-ll-ketotestosteronepropionate.

enemas Example -1 0-nownethy'lJI-ketotestosterone- Hydrolysis of-normethyl-1l-ketotestosterone propionate with potassium hydlgoxide.:in. aqueous methanol in the same manner as given in Example 3 resultedin 10- normethyl-1-lketotestosterone.

In the same manner as given in Example 4,1-0-normethyl-1l-ketotestosterone fol-mate, '1'0-normcthy1-11-ketotestosterone acetate, 10 nor-methyl l l ketotestosterone, but-yrate,10-normethyl-'ll-ketotestosterone isobutyrate,10-normethyl-1l-ketotestosterone valerate, l0-normethyl-ll-ketotestosterone isovalerate,l0-normethylll-ketotestosterone hexanoate,10-normethyl-ll-ketotestosterone heptanoate, IO-norrnethyl-ll-ketotestosterone octanoate, lO-normethyl-ll-ketotestosteronefi-cyclopentylpropionate, ate, lO-normethyl-ll-ketotestosterone phenylacetate and other like esters may be prepared by reaction of thecorresponding lO-normethybll-hydroxytestosterone-17-ester with chromicanhydride in acetic acid or with an acidified dichromatesolution. These'lotnorrnethyl-ll-ketotcstosterone-l7--csters, when treated withalcoholic alkali hydroxide in the same manner as. given in Example 3,yield lO-normethyl-l l-ketotestosterone.

it is to be understood that the invention is not to be limited to theexact details or exact compounds shown and described as obviousmodifications and equivalents will be apparent to one skilled in theart, and the invention is therefore to be limited only by the scope ofthe appended claims.

We claim:

. l. A steroid compound represented by the following formula:

wherein R is selected from the group consisting of hydrogen and methyland wherein R is selected from the group consisting of hydrogenand theacyl radical of a hydrocarbon carboxylic acid containing from one toeight carbon atoms, inclusive.

2. ll-ketotestosterone.

3. l-O-normethyl-ll-ketotestosterone.

4. l1-kctotestosterone-17-esters wherein the 17-ester group is O- C,O.R,wherein R is a lower-alkyl radical.

lO-normethyl-ll-ketotestosterone .benzo- 8 boxylic acid containing fromone to eight carbon atoms inclusive, with chromic aeid to obtain thecorresponding ll ketotestoste-rone ester.

9. In a process for the production of a compound selected from the groupconsisting of ll-ketotestosterone, l0-normethyl-l=l-ketotestosterone,and 17-esters thereof, the steps which include: treating a compoundselected from the group consisting of IIB-hydroxy-17-acyloxytestosteroneand l-O-norrnethyl-llfi-hydroxy-l7-acyloxytestostcrone, wherein the17-acyloXy groups are of the formuia AcO, Ac being the acyl radical ofan organic carboxylic acid containing from one to eight carbon atomsinclusive, with chromic acid to obtain the correspondingll-ketotestosterone ester, and contacting the ll-ketotestosteronc esterwith a base insolution to obtain the corresponding ll-ketotestosterone.

10. In a process for the production of ll-kctotestosT- teroneand17-esters thereof, the steps which include: treating allti-hydroxy-17-acyloxytestosterone, wherein the l-7-acyloxy groups areof the formula AcO, Ac being the acyl radical of an organic carboxylicacid containing from one to eight carbon atoms, inclusive, with chromicacid to obtain the corresponding ll-ketotes tosterone ester, andcontacting the ll-ketotestosterone ester with a base in solution toobtain ll-ketotestosterone. 7

11. In a process for the production of IO-normethylll-ketotestosteroneand 17-esters thereof, the steps which include: treating a IO-nrmethyI-l1fl-l1ydroxy-17-acyloxytestosterone, wherein the 17-acyloxygroups are of t f mula A O; c being e y ra c l of n Organic carboxylicacid containing from one to eight carbon atoms, inclusive, with chromicacid to obtain the corresponding ;11 -ket0te stosteron e ester, andcontacting the in which R is the acyl group of a hydrocarbon carboxylicacid containing from one to eight carbon atoms.

N0 references cited.

1. A STERIOD COMPOUND REPRESENTED BY THE FOLLOWING FORMULA: